Genetically Unstable CXG Repeats are Structurally Dynamic and Have a High Propensity for Folding. An NMR and UV Spectroscopic Study

Zheng, Minxue; Huang, Xuening; Smith, Geoff; Yang, Xiu Juan; Gao, Xiaolian

doi:10.1006/jmbi.1996.0643

Cited by 88 publications

(68 citation statements)

References 26 publications

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“…Early studies of expandable repeats suggested their unusual structural potential (133,205,230,231,238,307,308). Single-stranded d(CGG) n , d(CCG) n , d(CTG) n , and d(CAG) n stretches can fold into hairpin-like structures stabilized by both WC and non-WC base pairs (36,72,180,311). Hairpins formed by the above four repeats differ in the nature of non-WC base pairs.…”

Section: Unusual Dna Structuresmentioning

confidence: 99%

Replication Fork Stalling at Natural Impediments

Mirkin

2007

Microbiol Mol Biol Rev

446

460

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SUMMARY Accurate and complete replication of the genome in every cell division is a prerequisite of genomic stability. Thus, both prokaryotic and eukaryotic replication forks are extremely precise and robust molecular machines that have evolved to be up to the task. However, it has recently become clear that the replication fork is more of a hurdler than a runner: it must overcome various obstacles present on its way. Such obstacles can be called natural impediments to DNA replication, as opposed to external and genetic factors. Natural impediments to DNA replication are particular DNA binding proteins, unusual secondary structures in DNA, and transcription complexes that occasionally (in eukaryotes) or constantly (in prokaryotes) operate on replicating templates. This review describes the mechanisms and consequences of replication stalling at various natural impediments, with an emphasis on the role of replication stalling in genomic instability.

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Section: Unusual Dna Structuresmentioning

confidence: 99%

Replication Fork Stalling at Natural Impediments

Mirkin

2007

Microbiol Mol Biol Rev

446

460

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“…Similar to hairpins, the triplex structures mediate intergenerational instability in 96% of transmissions in FRDA patients [35]. Several structures have been reported for CGG and CCG and more complex minisatellites [such as telomeres] including i-motif [39], e-motif [40] and quadruplex DNA [41].…”

Section: Stable Hydrogen Bonding Blocks Repair Of Hairpin Loops mentioning

confidence: 99%

Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease

McMurray

2008

DNA Repair

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Mammalian cells have evolved sophisticated DNA repair systems to correct mispaired or damaged bases and extrahelical loops. Emerging evidence suggests that, in some cases, the normal DNA repair machinery is "highjacked" to become a causative factor in mutation and disease, rather than act as a safeguard of genomic integrity. In this review, we consider two cases in which active MMR leads to mutation or to cell death. There may be similar mechanisms by which uncoupling of normal MMR recognition from downstream repair allows triplet expansions underlying human neurodegenerative disease, or cell death in response to chemical lesion.

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“…1). Physical, biochemical, and theoretical approaches have clearly demonstrated a propensity for forming hairpins by single strands of CTG, CAG, CCG, CGG, GTC and GAC Gacy et al, 1995;Mitas et al, 1995;Yu et al, 1995aYu et al, , 1995bMariappan et al, 1996aMariappan et al, , 1996bPetruska et al, 1996;Zheng et al, 1996;Mitas, 1997;Ohshima and Wells, 1997;Yu S, et al, 1997;Gacy and McMurray, 1998;Mariappan et al, 1998aMariappan et al, , 1998b. Stable hairpins are not observed under physiological conditions with other trinucleotide repeats or DNA sequences with a non-repetitive but otherwise identical base composition (Gacy et al, 1995;Gacy and McMurray, 1998).…”

Section: Structural Features Of Trinucleotide Repeat Dnamentioning

confidence: 99%

Trinucleotide repeat instability: a hairpin curve at the crossroads of replication, recombination, and repair

Lenzmeier

Freudenreich

2003

Cytogenet Genome Res

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The trinucleotide repeats that expand to cause human disease form hairpin structures in vitro that are proposed to be the major source of their genetic instability in vivo. If a replication fork is a train speeding along a track of double-stranded DNA, the trinucleotide repeats are a hairpin curve in the track. Experiments have demonstrated that the train can become derailed at the hairpin curve, resulting in significant damage to the track. Repair of the track often results in contractions and expansions of track length. In this review we introduce the in vitro evidence for why CTG/CAG and CCG/CGG repeats are inherently unstable and discuss how experiments in model organisms have implicated the replication, recombination and repair machinery as contributors to trinucleotide repeat instability in vivo.

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Genetically Unstable CXG Repeats are Structurally Dynamic and Have a High Propensity for Folding. An NMR and UV Spectroscopic Study

Cited by 88 publications

References 26 publications

Replication Fork Stalling at Natural Impediments

Replication Fork Stalling at Natural Impediments

Hijacking of the mismatch repair system to cause CAG expansion and cell death in neurodegenerative disease

Trinucleotide repeat instability: a hairpin curve at the crossroads of replication, recombination, and repair

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